Key result
Recombinant human ACE2 (2.0 mg/kg/day) decreased body weight, improved glucose metabolism, and induced browning of white adipose tissue in high-fat diet-fed mice.
Why the study?
Because ACE2 counteracts the pro-obesity ANG II/AT1R axis by converting ANG II to Ang 1-7, the authors hypothesized that ACE2 exerts a strong anti-obesity effect by increasing Ang 1-7 levels.
Does recombinant human ACE2 reduce body weight and improve glucose metabolism in high-fat diet-induced obesity mice?
Does recombinant human ACE2 reduce body weight and improve glucose metabolism in high-fat diet-induced obesity mice?
Recombinant human ACE2 exerts anti-obesity effects by stimulating brown adipose tissue and inducing browning in white adipose tissue in a mouse model of diet-induced obesity.
Does not support clinical use in obesity or diabetes; leaves open translation of rhACE2 metabolic effects to humans.
The angiotensin II (ANG II)-ANG II type 1 receptor (AT1R) axis is a key player in the pathophysiology of obesity. Angiotensin-converting enzyme 2 (ACE2) counteracts the ANG II/AT1R axis via converting ANG II to angiotensin 1–7 (Ang 1–7), which is known to have an anti-obesity effect. In this study, we hypothesized that ACE2 exerts a strong anti-obesity effect by increasing Ang 1–7 levels. We injected intraperitoneally recombinant human ACE2 (rhACE2, 2.0 mg·kg−1·day−1) for 28 days to high-fat diet (HFD)-induced obesity mice. rhACE2 treatment decreased body weight and improved glucose metabolism. Furthermore, rhACE2 increased oxygen consumption and upregulated thermogenesis in HFD-fed mice. In the rhACE2 treatment group, brown adipose tissue (BAT) mass increased, accompanied with ameliorated insulin signaling and increased protein levels of uncoupling protein-1 (UCP-1) and PRD1-BF1-RIZ1 homologous domain containing 16. Importantly, subcutaneous white adipose tissue (sWAT) mass decreased, concomitant with browning, which was established by the increase of UCP-1 expression. The browning is the result of increased H3K27 acetylation via the downregulation of histone deacetylase 3 and increased H3K9 acetylation via upregulation of GCN5 and P300/CBP-associated factor. These results suggest that rhACE2 exerts anti-obesity effects by stimulating BAT and inducing browning in sWAT. ACE2 and the Ang 1–7 axis represent a potential therapeutic approach to prevent the development of obesity.
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Kawabe et al. (2019) studied High-fat diet (HFD)-induced obesity. recombinant human ACE2 (rhACE2) was evaluated. Recombinant human ACE2 (2.0 mg/kg/day) decreased body weight, improved glucose metabolism, and induced browning of white adipose tissue in high-fat diet-fed mice.
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